BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBO...BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains unknown.Hence,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun.METHODS:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)groups.In the cREBOA and C-pREBOA groups,the balloon was inflated for 60 min.The hemodynamic and laboratory values were compared at various observation time points.Tissue samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin staining.RESULTS:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent hemorrhage.Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.展开更多
Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have...Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.展开更多
AIM To compare the effects of extract F of red-rooted Salvia (EFRRS) on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock and reperfusion in rats.``METHODS The rats were subject to hemorrhagic ...AIM To compare the effects of extract F of red-rooted Salvia (EFRRS) on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock and reperfusion in rats.``METHODS The rats were subject to hemorrhagic shock and followed by reperfusion, and were divided randomly into two groups. Group 1 received saline, and group 2received EFRRS intravenously. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesional area in the corpus or antrum. The degree of gastric mucosal lesions (DGML) was catalogued grade 0,1. 2 and 3. The concentrations of prostaglandins (lags)were measured by radioimmunoassay. The concentration of MDA was measured according to the procedures of Asakawa. The activity of SOD was measured by the biochemical way. The growth rates or inhibitory rates of above-mentioned parametes were calculated.``RESULTS As compared with IGML (%), grade 3 damage (%) and MDA content (nmol/g tissue) of gastric antrum which were respectively 7.96 ± 0.59, 34.86± 4.96 and 156.98± 16.12. those of gastric corpus which were respectively 23.18 ± 6.82, 58.44 ± 9.07 and 230.56 ± 19.37increased markedly (P<0.01), whereas the grade 0damage, grade 1 damage, the concentrations of PGE2 and PGI2(pg/ mg tissue), the ratio of PGI2/ TXA2 and the activity of SOD (U/ g tissue) of corpus which were respectively 3.01 _- 1.01, 8.35 + 1.95, 540.48 _+ 182.78,714.38 ± 123.74, 17.38 ± 5.93 and 134.29 ± 13.35 were markedly lower than those of antrum which were respectively 13.92 ± 2.25, 26.78 ± 6.06, 2218.56 ± 433.12,2531.76 ± 492.35, 43.46 ± 8.51 and 187.45 ± 17.67( P<0.01 ) after hemorrhagic shock and reperfusion. After intravenous EFRRS, the growth rates (%) of grade 0damage, grade 1 damage, the concentrations of PGE2 and PGI2, the ratio of PGI2/TXA2 and the activity of SOD of corpus which were respectively 632.56, 308.62, 40.75,74.75, 92.29 and 122.25 were higher than those in antrum which were respectively 104,89, 58.40, 11.12, 56.58,30.65 and 82.64, whereas the inhibitory rates (%) ofIGML, grade 3 damage and MDA content of gastric corpus were 82.93, 65.32 and 59.09, being higher than those of gastric antrum which were 76.64, 53.18 and 42.37.``CONCLUSION After hemorrhagic shock-reperfusion, the gastric mucosal lesions in the corpus were more severe than those in the antrum, which were related not only to the different distribution of endogenous PGs in the mucosa, but also to the different ability of anti-oxidation of the mucosa. The protective effect of EFRRS on the gastric mucosa in the corpus was more evident than that in the antrum, which was related to higher growth degree of PGs contents and anti-oxitative ability in gastric corpus after administration of EFRRS.展开更多
Artificial intelligence(AI),a branch of machine learning(ML)has been increasingly employed in the research of trauma in various aspects.Hemorrhage is the most common cause of trauma-related death.To better elucidate t...Artificial intelligence(AI),a branch of machine learning(ML)has been increasingly employed in the research of trauma in various aspects.Hemorrhage is the most common cause of trauma-related death.To better elucidate the current role of AI and contribute to future development of ML in trauma care,we conducted a review focused on the use of ML in the diagnosis or treatment strategy of traumatic hemorrhage.A literature search was carried out on PubMed and Google scholar.Titles and abstracts were screened and,if deemed appropriate,the full articles were reviewed.We included 89 studies in the review.These studies could be grouped into five areas:(1)prediction of outcomes;(2)risk assessment and injury severity for triage;(3)prediction of transfusions;(4)detection of hemorrhage;and(5)prediction of coagulopathy.Performance analysis of ML in comparison with current standards for trauma care showed that most studies demonstrated the benefits of ML models.However,most studies were retrospective,focused on prediction of mortality,and development of patient outcome scoring systems.Few studies performed model assessment via test datasets obtained from different sources.Prediction models for transfusions and coagulopathy have been developed,but none is in widespread use.AI-enabled ML-driven technology is becoming integral part of the whole course of trauma care.Comparison and application of ML algorithms using different datasets from initial training,testing and validation in prospective and randomized controlled trials are warranted for provision of decision support for individualized patient care as far forward as possible.展开更多
The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overloa...The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overload,and axonal degeneration.Cyclophilin D is an important component of the mitochondrial permeability transition pore.Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear.In this study,we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice,in which pyramidal neurons and axons express yellow fluorescent protein.We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin.We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening.We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage.We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury.In addition,inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage.Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage;inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage.Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.展开更多
BACKGROUND: Conventional neuroimaging diagnosis does not assist with the monitoring or evaluation of basal nuclei ischemic and hemorrhagic stroke, or motor functional recovery. Magnetic resonance, diffusion tensor im...BACKGROUND: Conventional neuroimaging diagnosis does not assist with the monitoring or evaluation of basal nuclei ischemic and hemorrhagic stroke, or motor functional recovery. Magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography have all been used to observe features of cerebral white matter fibrous structures. In addition, diffusion tensor tractography is the only non-invasive imaging method to display the corticospinal tract in vivo. OBJECTIVE: To evaluate the impairment degree of corticospinal tract induced by basal nuclei ischemic and hemorrhagic stroke through the use of magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography, and to analyze the correlation to muscular strength. DESIGN, TIME AND SETTING: A retrospective case analysis was performed at the Department of Medical Imaging, Neurology and Neurosurgery, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA between November 2002 and June 2008. PARTICIPANTS: A total of 15 patients with acute or subacute cerebral ischemic stroke and nine with hemorrhagic stroke in the basal nuclei were selected. METHODS: Magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography results and data were analyzed. Fractional anisotropy and directionally encoded color maps were obtained. Three-dimensional tractography of bilateral corticospinal tract was created, and corticospinal tract integrity was graded. Fractional anisotropy of infarct region and corresponding contralateral normal regions were measured, and hematoma volume in hemorrhagic stroke patients was determined. Hand motor function ability was evaluated using Brunstorm criteria. MAIN OUTCOME MEASURES: Fractional anisotropy of infarct region and corresponding contralateral normal regions; hematoma volume in hemorrhagic stroke patients; correlation between muscular strength and corticospinal tract impairment degree in ischemic stroke and hemorrhagic stroke patients before and after treatment. RESULTS: In ischemic stroke patients, the fractional anisotropy value was significantly lower in the infarct area of white matter than in the normal hemisphere (P 〈 0.01). The impairment degree of corticospinal tract negatively correlated with muscular strength of the corresponding hand (r = -0.97 P 〈 0.01). The hematoma volume of hemorrhagic stroke patients significantly negatively correlated with Spearman test results for muscular strength of the corresponding hand (r = -0.88, P 〈 0.01). CONCLUSION: Corticospinal tract impairment severity negatively correlated with muscular strength and motor functional recovery, which suggested that diffusion tensor imaging and diffusion tensor tractography could be used to evaluate corticospinal tract motor function.展开更多
Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Re...Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.展开更多
Diffuse axonal injury(DAI)is axonal and small vessel injury produced by a sudden acceleration of the head by an external force,and is a major cause of death and severe disability(Paterakis et al.,2000).Prognosis i...Diffuse axonal injury(DAI)is axonal and small vessel injury produced by a sudden acceleration of the head by an external force,and is a major cause of death and severe disability(Paterakis et al.,2000).Prognosis is poorer in patients with apparent hemorrhage than in those without(Paterakis et al.,2000).Therefore,it is important to identify the presence and precise position of hemorrhagic foci for a more accurate diagnosis.CT and magnetic resonance imaging(MRI)have long been applied in the diagnosis of DAI, but they are not sensitive enough for the detection of small hemorrhagic foci, and cannot meet the requirements for early diagnosis. A major advance in MRI has been the development of susceptibility weighted imaging (SWI), which has greatly increased the ability to detect small hemorrhagic foci after DAI (Ashwal et al., 2006).展开更多
AIM: To study the protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats.METHODS: A total of 32 SD rats were randomly divided into four g...AIM: To study the protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats.METHODS: A total of 32 SD rats were randomly divided into four groups (n = 8, each group): normal group,model group, low dosage group (treated with 10 g/kg Astragalus membranaceus) and high dosage group (treated with 20 g/kg Astragalus membranaceus). The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution (3 mL)was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid (LD), nitric oxide (NO),endothelin-1 (ET-1), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) in intestinal mucosa were determined.RESULTS: The intestinal mucosa pathology showed severe damage in model group and low dosage group,slight damage in high dosage group and no obvious damage in normal group. The Chiu's score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group.CONCLUSION: High dose Astragalus membranaeus has much better protective effect on hemorrhagic shockreperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.展开更多
AIM: To observe the gastric mucosal injury caused by hemorrhagic shock and reperfusion and to compare the effect between Salvia miltiorrhizae extract F (SEF) and cimetidine (CI) on it.METHODS: A model of hemorrhage/re...AIM: To observe the gastric mucosal injury caused by hemorrhagic shock and reperfusion and to compare the effect between Salvia miltiorrhizae extract F (SEF) and cimetidine (CI) on it.METHODS: A model of hemorrhage/reperfusion injury was produced by Itoh method. Wistar rats were randomly divided into three groups: 0.9% sodium chloride treatment group (NS group), SEF treatment group (SEF group), and CI treatment group (CI group). Saline, SEF and CI were injected respectively. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesion area in the gastric mucosa. The degree of gastric mucosal lesions was categorized into grades 0, 1, 2, 3. Atom absorption method was used to measure the intracellular calcium content. Radioimmunoassay was used to measure the concentrations of prostaglandins.RESULTS: IGML (%) and grade 3 (%) were 23.18±6.82, 58.44±9.07 in NS group, 4.42±1.39, 20.32±6.95 in SEF group and 3.74±1.56, 23.12±5.09 in CI group, and theabove parameters in SEF group and CI group decreased significantly (IGML: SEF vs NS, t = 6.712, P = 0.000<0.01; CI vs NS, t= 6.943, P= 0.000<0.01; grade 3: SEF vs NS,t= 8.386, P= 0.000; CI vs NS, t= 8.411, P= 0.000), but the grade 0 and grade 1 damage in SEF group (22.05±5.96, 34.12±8.12) and CI group (18.54±4.82, 30.15±7.12) were markedly higher than those in NS group (3.01±1.01, 8.35±1.95; grade 0: SEF vs NS, t= 8.434,P = 0.000<0.01; CI vs NS, t = 7.950, P = 0.000<0.01;grade 1: SEF vs NS, t= 8.422, P= 0.000<0.01; CI vs NS,t = 8.448, P = 0.000<0.01). The intracellular calcium content (μg/mg) in SEF group (0.104±0.015) and CI group (0.102±0.010) was markedly lower than that in NS group(0.131±0.019, SEF vs NS, t= 2.463, P= 0.038<0.05; CIvs NS, t= 3.056, P= 0.017<0.05). The levels (pg/mg) ofPGE2, 6-keto-PGF1αand 6-keto-PGF1α/TXB2 were 540±183, 714±124, 17.38±5.93 in NS group and 581±168, 737±102, 19.04±8.03 in CI group, 760±192, 1 248±158, 33.42±9.24 in SEF group, and the above parameters in SEF group markedly raised (PGE2: SEF vs NS, t = 2.282, P = 0.046 <0.05; SEF vs CI, t = 2.265, P = 0.047<0.05; 6-ketoPGF1α: SEF vsNS, t= 6.583, P= 0.000<0.000; SEF vsCI,t = 6.708, P = 0.000<0.01; 6-keto-PGF1α/TXB2: SEF vs NS, t= 3.963, P= 0.003<0.001; SEF vs CI, t= 3.243,P = 0.009<0.01), whereas TXB2 level in SEF group (45.37±7.54) was obviously lower than that in NS group (58.28±6.74, t = 3.086, P = 0.014<0.05) and CI group (54.32±6.89, t = 2.265, P = 0.047<0.05). No significant difference was shown between NS group and CI group (PGE2: t= 0.414, P= 0.688>0.05; 6-keto-PGF1α: t= 0.310,P = 0.763>0.05; TXB2: t = 1.099, P = 0.298>0.05; 6-keto-PGF1α/TXB2: t = 0.372, P = 0.718>0.05).CONCLUSION: Both SEF and CI could inhibit reperfusion induced injury in gastric mucosa, but with different mechanisms. SEF could not only enhance the protective effect of gastric rnucosa, but also abate the injury factors, while CI can only abate the injury factors.展开更多
Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,g...Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.展开更多
Objective: It demonstrates the correlation of the viral hemorrhagic fever with kidney failure and the treatment as well as the outcome. Method: A PubMed search of the English literature from 1999 to 2019 was performed...Objective: It demonstrates the correlation of the viral hemorrhagic fever with kidney failure and the treatment as well as the outcome. Method: A PubMed search of the English literature from 1999 to 2019 was performed using “viral hemorrhagic fever, Case Report, Renal Failure” as the subject. The inclusion criteria were the following: 1) case report and case series of two or more patients;2) the report detailed the clinical presentation and reported the status of the renal system;3) the report described the management of renal failure if any;and 4) the etiology of the infection is known and is one of the known agents of viral hemorrhagic fever, listed on the centers of disease control website. We excluded infections related to vaccination related to viral hemorrhagic fever. Result: We found the mean age of these patients was 41.5. The male to female ratio was about 3.5:1. Dengue and Hantaviruses constituted 70.5% of patients. The overall mortality of the study cohort was 32.2%. Half of the patients had acute kidney injury and required renal replacement therapy. The chi-square statistic is 0.41;The p-value is 0.51;The chi-square statistic is 6.4254. Overall mortality was 32.3% in one cohort of 78 patients. The illness goes through several stages [1] [2] of clinical features and some viruses in the group have a high case fatality rate. Conclusions: Early diagnosis with aggressive supportive care is critical for improving clinical outcomes. Renal involvement is common. Amongst the cohort reviewed, of patients who had acute kidney injury, half of the patients required renal replacement support. However, some viruses cause greater kidney injury than others, for instance, kidney injury is more severe in Dengue hemorrhagic fevers when compared to Hantaviruses. Simultaneous management of public health by prevention and control of outbreaks is particularly important.展开更多
Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits we...Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits were made into hemorrhagic shock,then reperfused with different liquids.These rabbits were divided by random number table into three groups:sham operation group(Sham group),reperfusion with normal saline group(NS group),reperfusion with 1%GLP group(LS group).Bacterial translocation of blood and TNF-αcontent in serum were respectively observed at the time before shock,40 min after shock,40 min and 90 min after.TNF-αcontent in intestinal mucosa and the degree of intestinal mucosal injury were examined at 90 min post-resuscitation.Results 1 With the extension of reperfusion time,the positive rate of blood bacteria increased gradually in NS group,which was significantly higher than that of Sham group and LS group(P<0.05),meanwhile the degree of intestinal mucosal injury in NS group was more severe than that of Sham group and LS group too(P<0.05).2TNF-αcontent in serum of NS group and LS group were increased obviously compared with that before shock and in Sham group(P<0.05).TNF-αcontent in serum was further increased after reperfusion with NS,which was distinctly higher than that in LS group.TNF-αcontent in intestinal mucosa of NS group was significantly higher than that in LS group and Sham group too(P<0.05).Conclusion GLP can protect intestinal mucosa against HS-R injury,and its effects may relate with the change of TNF-αin hemorrhagic shock rabbits.展开更多
AIM: To study the effect of albumin administration on lung injury in trauma/hemorrhagic shock (T/HS). METHODS: Sixty experimental animals were randomly divided into three groups: rats undergoing laparotomy without sho...AIM: To study the effect of albumin administration on lung injury in trauma/hemorrhagic shock (T/HS). METHODS: Sixty experimental animals were randomly divided into three groups: rats undergoing laparotomy without shock (T/SS); rats with T/HS and resuscitation with blood plus twice the volume of shed blood as Ringer’s lactate (RL), and rats with T/HS and resuscitation with blood plus additional 3 mL of 50 g/L human albumin. Expression of polymorphonuclear neutrophil (PMN) CD11b/CD18, intercellular adhesion molecule-1 (ICAM-1) of jugular vein blood and the severity of lung injuries [determined mainly by measuring activity of lung tissue myeloperoxidase (MPO) and lung injury score (LIS)] were measured after a 3-h recovery period. RESULTS: All three groups showed a significant difference in the expressions of CD11b/CD18, ICAM-1, and severity of lung injury. The expressions of CD11b/ CD18 in T/SS group, T/HS + RL group, T/HS + albumin group were 17.76% ± 2.11%, 31.25% ± 3.48%, 20.36% ± 3.21%, respectively (F = 6.25, P < 0.05). The expressions of ICAM-1 (U/mL) in T/SS group, T/ HS + RL group, T/HS + albumin group were 258.76 ± 98.23, 356.23 ± 65.6, 301.01 ± 63.21, respectively (F = 5.86, P < 0.05). The expressions of MPO (U/g) in T/SS group, T/HS + RL group, T/HS + albumin group were 2.53 ± 0.11, 4.63 ± 1.31, 4.26 ± 1.12, respectively (F = 6.26, P < 0.05). Moreover, LIS in T/HS + RL group, T/HS + albumin group was 2.62 ± 0.23, 1.25 ± 0.24, respectively. The expressions of CD11b/CD18, ICAM-1 and MPO in T/HS + RL group were significantly increased compared to T/SS group (P = 0.025, P = 0.036, P = 0.028,respectively). However, administration of 3 mL of 50 g/L albumin significantly down-regulated the expressions of CD11b/CD18, ICAM-1 and lung injury index (MPO and LIS) when compared with the T/HS + RL rats (P = 0.035, P = 0.046, P = 0.038, P = 0.012, respectively). CONCLUSION: The infusion of albumin during resuscitation period can protect lung from injury and decrease the expressions of CD11b/CD18, ICAM-1 in T/ HS rats.展开更多
Objective:The objective of this study was to investigate the effects and possible mechanisms of action of ginseng on cerebral vasospasm and early brain injury(EBI)following hemorrhagic stroke.Materials and Methods:Spr...Objective:The objective of this study was to investigate the effects and possible mechanisms of action of ginseng on cerebral vasospasm and early brain injury(EBI)following hemorrhagic stroke.Materials and Methods:Sprague-Dawley(SD)rats(n=48)were randomly divided into sham operation(sham group),subarachnoid hemorrhage(SAH)model(SAH group),normal saline(NS group),and Ginaton(Extract of Ginkgo Biloba Leaves Drops)intervention(gin group)groups.MCP-1 m RNA and tumor necrosis factor levels were detected using reverse transcription-polymerase chain reaction.The relative expression of m RNA was detected by Western blotting.Results:(1)Compared with the sham group,the SAH,NS,and gin groups had different degrees of neurological dysfunction.Compared with the SAH and NS groups,the neurological deficits in the gin group were significantly improved(P<0.05).(2)Compared with the sham group,the relative expression levels of MCP-1 m RNA in the SAH,NS,and gin groups were 5.1±0.9,3.4±0.6,and 2.5±0.4,respectively;the relative expression levels of m RNA were 13.3±2.4,11.2±1.8,and 3.8±0.6,respectively.(3)The apoptosis rates of brain tissue in the sham,SAH,NS,and gin groups were 4.8±0.7,54.2±10.3,50.1±7.4,and 28.4±4.5,respectively.(4)Western blot showed that the relative expression levels of toll-like receptor-4(TLR-4)protein in the sham,SAH,NS,and gin groups were 0.29±0.03,0.87±0.15,0.65±0.13,and 0.41±0.17,respectively;the relative expression levels of B protein were 0.21±0.04,0.96±0.14,0.73±0.18,and 0.30±0.05,respectively.Gin treatment could inhibit TLR-4 and nuclear factor-κB(NF-κB)protein expression.Conclusions:Dona tablets may inhibit activation of the NF-κB signaling pathway,and SAH-induced inflammatory response,so as to reduce cerebral vasospasm and EBI.展开更多
Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury(EBI).In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,p...Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury(EBI).In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,poor initial clinical grades,and some radiographic findings are used,but these markers are somewhat subjective.Thus,it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications.In our opinion,an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia(DCI),being a therapeutic target,and can be measured easily in the peripheral blood in an acute stage.A good candidate of such a biomarker is a matricellular protein,which is a secreted,inducible and multifunctional extracellular matrix protein.There are many kinds of matricellular proteins reported,but only tenascin-C,osteopontin,galectin-3 and periostin are reported relevant to EBI and DCI.Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI,and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI.This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted.展开更多
The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not b...The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage.Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham(injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1(rhwnt1), small interfering Wnt1(siwnt1) RNA, and monoclonal antibody of Frizzled1(anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, β-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and β-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury(within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of β-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines(interleukin-1β, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC,Division of Life Sciences and Medicine, University of Science and Technology of China(approval No. LLSC-20180202) in May 2017.展开更多
Early brain injury(EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage(SAH). This study investigated the role of glucose-regulated protein 78(GRP78) in EBI after SAH. Male Sprague-Dawley rats(n...Early brain injury(EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage(SAH). This study investigated the role of glucose-regulated protein 78(GRP78) in EBI after SAH. Male Sprague-Dawley rats(n=108) weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated d UTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.展开更多
The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to p...The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.展开更多
基金supported by military logistics scientific research project(AHJ16J004)。
文摘BACKGROUND:Resuscitative endovascular balloon occlusion of the aorta(REBOA)can temporarily control traumatic bleeding.However,its prolonged use potentially leads to ischemia-reperfusion injury(IRI).Partial REBOA(pREBOA)can alleviate ischemic burden;however,its security and eff ectiveness prior to operative hemorrhage control remains unknown.Hence,we aimed to estimate the effi cacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun.METHODS:Twenty Landrace pigs were randomized into control(no aortic occlusion)(n=5),intervention with complete REBOA(cREBOA)(n=5),continuous pREBOA(C-pREBOA)(n=5),and sequential pREBOA(S-pREBOA)(n=5)groups.In the cREBOA and C-pREBOA groups,the balloon was inflated for 60 min.The hemodynamic and laboratory values were compared at various observation time points.Tissue samples immediately after animal euthanasia from the myocardium,liver,kidneys,and duodenum were collected for histological assessment using hematoxylin and eosin staining.RESULTS:Compared with the control group,the survival rate of the REBOA groups was prominently improved(all P<0.05).The total volume of blood loss was markedly lower in the cREBOA group(493.14±127.31 mL)compared with other groups(P<0.01).The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups(P<0.05).At 120 min,the S-pREBOA group showed higher alanine aminotransferase(P<0.05)but lower blood urea nitrogen compared with the cREBOA group(P<0.05).CONCLUSION:In this trauma model with liver injury,a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure,despite persistent hemorrhage.Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures,and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.
基金supported the National Natural Science Foundation of China,No.81974178(to CD).
文摘Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.
基金Supported by the National Natural Science Foundation of China.No.3870890
文摘AIM To compare the effects of extract F of red-rooted Salvia (EFRRS) on mucosal lesions of gastric corpus and antrum induced by hemorrhagic shock and reperfusion in rats.``METHODS The rats were subject to hemorrhagic shock and followed by reperfusion, and were divided randomly into two groups. Group 1 received saline, and group 2received EFRRS intravenously. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesional area in the corpus or antrum. The degree of gastric mucosal lesions (DGML) was catalogued grade 0,1. 2 and 3. The concentrations of prostaglandins (lags)were measured by radioimmunoassay. The concentration of MDA was measured according to the procedures of Asakawa. The activity of SOD was measured by the biochemical way. The growth rates or inhibitory rates of above-mentioned parametes were calculated.``RESULTS As compared with IGML (%), grade 3 damage (%) and MDA content (nmol/g tissue) of gastric antrum which were respectively 7.96 ± 0.59, 34.86± 4.96 and 156.98± 16.12. those of gastric corpus which were respectively 23.18 ± 6.82, 58.44 ± 9.07 and 230.56 ± 19.37increased markedly (P<0.01), whereas the grade 0damage, grade 1 damage, the concentrations of PGE2 and PGI2(pg/ mg tissue), the ratio of PGI2/ TXA2 and the activity of SOD (U/ g tissue) of corpus which were respectively 3.01 _- 1.01, 8.35 + 1.95, 540.48 _+ 182.78,714.38 ± 123.74, 17.38 ± 5.93 and 134.29 ± 13.35 were markedly lower than those of antrum which were respectively 13.92 ± 2.25, 26.78 ± 6.06, 2218.56 ± 433.12,2531.76 ± 492.35, 43.46 ± 8.51 and 187.45 ± 17.67( P<0.01 ) after hemorrhagic shock and reperfusion. After intravenous EFRRS, the growth rates (%) of grade 0damage, grade 1 damage, the concentrations of PGE2 and PGI2, the ratio of PGI2/TXA2 and the activity of SOD of corpus which were respectively 632.56, 308.62, 40.75,74.75, 92.29 and 122.25 were higher than those in antrum which were respectively 104,89, 58.40, 11.12, 56.58,30.65 and 82.64, whereas the inhibitory rates (%) ofIGML, grade 3 damage and MDA content of gastric corpus were 82.93, 65.32 and 59.09, being higher than those of gastric antrum which were 76.64, 53.18 and 42.37.``CONCLUSION After hemorrhagic shock-reperfusion, the gastric mucosal lesions in the corpus were more severe than those in the antrum, which were related not only to the different distribution of endogenous PGs in the mucosa, but also to the different ability of anti-oxidation of the mucosa. The protective effect of EFRRS on the gastric mucosa in the corpus was more evident than that in the antrum, which was related to higher growth degree of PGs contents and anti-oxitative ability in gastric corpus after administration of EFRRS.
基金Defence Research and Development Canada,Program Activity PEOPLE_014.
文摘Artificial intelligence(AI),a branch of machine learning(ML)has been increasingly employed in the research of trauma in various aspects.Hemorrhage is the most common cause of trauma-related death.To better elucidate the current role of AI and contribute to future development of ML in trauma care,we conducted a review focused on the use of ML in the diagnosis or treatment strategy of traumatic hemorrhage.A literature search was carried out on PubMed and Google scholar.Titles and abstracts were screened and,if deemed appropriate,the full articles were reviewed.We included 89 studies in the review.These studies could be grouped into five areas:(1)prediction of outcomes;(2)risk assessment and injury severity for triage;(3)prediction of transfusions;(4)detection of hemorrhage;and(5)prediction of coagulopathy.Performance analysis of ML in comparison with current standards for trauma care showed that most studies demonstrated the benefits of ML models.However,most studies were retrospective,focused on prediction of mortality,and development of patient outcome scoring systems.Few studies performed model assessment via test datasets obtained from different sources.Prediction models for transfusions and coagulopathy have been developed,but none is in widespread use.AI-enabled ML-driven technology is becoming integral part of the whole course of trauma care.Comparison and application of ML algorithms using different datasets from initial training,testing and validation in prospective and randomized controlled trials are warranted for provision of decision support for individualized patient care as far forward as possible.
基金supported by the National Natural Science Foundation of China,Nos.81901267(to YY),82001263(to WXC),81901193(to HLZ)a grant from State Key Laboratory of Trauma,Burn and Combined Injury,No.SKLYQ202002(to YJC)+1 种基金a grant from Wuxi Municipal Health Commission No.2020ZHYB19(to YY)a grant from Wuxi Science and Technology Bureau,No.Y20212045(to LKY)。
文摘The mitochondrial permeability transition pore is a nonspecific transmembrane channel.Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling,calcium overload,and axonal degeneration.Cyclophilin D is an important component of the mitochondrial permeability transition pore.Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear.In this study,we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice,in which pyramidal neurons and axons express yellow fluorescent protein.We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin.We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening.We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage.We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury.In addition,inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage.Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage;inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage.Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.
基金a Grant from the Science and Technology Department of Fujian Province,No.2006J0192
文摘BACKGROUND: Conventional neuroimaging diagnosis does not assist with the monitoring or evaluation of basal nuclei ischemic and hemorrhagic stroke, or motor functional recovery. Magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography have all been used to observe features of cerebral white matter fibrous structures. In addition, diffusion tensor tractography is the only non-invasive imaging method to display the corticospinal tract in vivo. OBJECTIVE: To evaluate the impairment degree of corticospinal tract induced by basal nuclei ischemic and hemorrhagic stroke through the use of magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography, and to analyze the correlation to muscular strength. DESIGN, TIME AND SETTING: A retrospective case analysis was performed at the Department of Medical Imaging, Neurology and Neurosurgery, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA between November 2002 and June 2008. PARTICIPANTS: A total of 15 patients with acute or subacute cerebral ischemic stroke and nine with hemorrhagic stroke in the basal nuclei were selected. METHODS: Magnetic resonance, diffusion tensor imaging, and diffusion tensor tractography results and data were analyzed. Fractional anisotropy and directionally encoded color maps were obtained. Three-dimensional tractography of bilateral corticospinal tract was created, and corticospinal tract integrity was graded. Fractional anisotropy of infarct region and corresponding contralateral normal regions were measured, and hematoma volume in hemorrhagic stroke patients was determined. Hand motor function ability was evaluated using Brunstorm criteria. MAIN OUTCOME MEASURES: Fractional anisotropy of infarct region and corresponding contralateral normal regions; hematoma volume in hemorrhagic stroke patients; correlation between muscular strength and corticospinal tract impairment degree in ischemic stroke and hemorrhagic stroke patients before and after treatment. RESULTS: In ischemic stroke patients, the fractional anisotropy value was significantly lower in the infarct area of white matter than in the normal hemisphere (P 〈 0.01). The impairment degree of corticospinal tract negatively correlated with muscular strength of the corresponding hand (r = -0.97 P 〈 0.01). The hematoma volume of hemorrhagic stroke patients significantly negatively correlated with Spearman test results for muscular strength of the corresponding hand (r = -0.88, P 〈 0.01). CONCLUSION: Corticospinal tract impairment severity negatively correlated with muscular strength and motor functional recovery, which suggested that diffusion tensor imaging and diffusion tensor tractography could be used to evaluate corticospinal tract motor function.
基金supported by the National Natural Science Foundation of China,Nos.82071382(to MZ),81601306(to HS)The Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(to MZ)+5 种基金Jiangsu 333 High-Level Talent Training Project(2022)(to HS)The Jiangsu Maternal and Child Health Research Key Project,No.F202013(to HS)Jiangsu Talent Youth Medical Program,No.QNRC2016245(to HS)Shanghai Key Lab of Forensic Medicine,No.KF2102(to MZ)Suzhou Science and Technology Development Project,No.SYS2020089(to MZ)The Fifth Batch of Gusu District Health Talent Training Project,No.GSWS2019060(to HS)。
文摘Intracerebral hemorrhage is a life-threatening condition with a high fatality rate and severe sequelae.However,there is currently no treatment available for intracerebral hemorrhage,unlike for other stroke subtypes.Recent studies have indicated that mitochondrial dysfunction and mitophagy likely relate to the pathophysiology of intracerebral hemorrhage.Mitophagy,or selective autophagy of mitochondria,is an essential pathway to preserve mitochondrial homeostasis by clearing up damaged mitochondria.Mitophagy markedly contributes to the reduction of secondary brain injury caused by mitochondrial dysfunction after intracerebral hemorrhage.This review provides an overview of the mitochondrial dysfunction that occurs after intracerebral hemorrhage and the underlying mechanisms regarding how mitophagy regulates it,and discusses the new direction of therapeutic strategies targeting mitophagy for intracerebral hemorrhage,aiming to determine the close connection between mitophagy and intracerebral hemorrhage and identify new therapies to modulate mitophagy after intracerebral hemorrhage.In conclusion,although only a small number of drugs modulating mitophagy in intracerebral hemorrhage have been found thus far,most of which are in the preclinical stage and require further investigation,mitophagy is still a very valid and promising therapeutic target for intracerebral hemorrhage in the long run.
基金supported by a grant from the Key Science and Technology Development Project of Nanjing Medical University in ChinaNo.08NMU054
文摘Diffuse axonal injury(DAI)is axonal and small vessel injury produced by a sudden acceleration of the head by an external force,and is a major cause of death and severe disability(Paterakis et al.,2000).Prognosis is poorer in patients with apparent hemorrhage than in those without(Paterakis et al.,2000).Therefore,it is important to identify the presence and precise position of hemorrhagic foci for a more accurate diagnosis.CT and magnetic resonance imaging(MRI)have long been applied in the diagnosis of DAI, but they are not sensitive enough for the detection of small hemorrhagic foci, and cannot meet the requirements for early diagnosis. A major advance in MRI has been the development of susceptibility weighted imaging (SWI), which has greatly increased the ability to detect small hemorrhagic foci after DAI (Ashwal et al., 2006).
基金Supported by the Chinese Traditional Medicine Foundation of Guangdong Province, China, No. 102061
文摘AIM: To study the protective effect of Astragalus membranaceus on intestinal mucosa reperfusion injury and its mechanism after hemorrhagic shock in rats.METHODS: A total of 32 SD rats were randomly divided into four groups (n = 8, each group): normal group,model group, low dosage group (treated with 10 g/kg Astragalus membranaceus) and high dosage group (treated with 20 g/kg Astragalus membranaceus). The model of hemorrhagic shock for 60 min and reperfusion for 90 min was established. Therapeutic solution (3 mL)was administrated before reperfusion. At the end of the study, the observed intestinal pathology was analyzed. The blood concentrations of lactic acid (LD), nitric oxide (NO),endothelin-1 (ET-1), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) in intestinal mucosa were determined.RESULTS: The intestinal mucosa pathology showed severe damage in model group and low dosage group,slight damage in high dosage group and no obvious damage in normal group. The Chiu's score in low dose group and high dose group was significantly lower than that in model group. The content of MDA in model group was higher than that in low and high dose groups, while that in high dose group was almost the same as in normal group. The activity of SOD and GSH-PX was the lowest in model group and significantly higher in high dose group than in normal and low dose groups. The concentrations of LD and ET-1 in model group were the highest. The concentrations of NO in model group and low dose group were significantly lower than those in high dose group and normal group.CONCLUSION: High dose Astragalus membranaeus has much better protective effect on hemorrhagic shockreperfusion injury of intestinal mucosa than low dose Astragalus membranaceus. The mechanism may be that Astragalus membranaceus can improve antioxidative effect and regulate NO/ET level during hemorrhagic reperfusion.
基金Supported by the National Natural Science Foundation of China, No. 3870890
文摘AIM: To observe the gastric mucosal injury caused by hemorrhagic shock and reperfusion and to compare the effect between Salvia miltiorrhizae extract F (SEF) and cimetidine (CI) on it.METHODS: A model of hemorrhage/reperfusion injury was produced by Itoh method. Wistar rats were randomly divided into three groups: 0.9% sodium chloride treatment group (NS group), SEF treatment group (SEF group), and CI treatment group (CI group). Saline, SEF and CI were injected respectively. The index of gastric mucosal lesions (IGML) was expressed as the percentage of lesion area in the gastric mucosa. The degree of gastric mucosal lesions was categorized into grades 0, 1, 2, 3. Atom absorption method was used to measure the intracellular calcium content. Radioimmunoassay was used to measure the concentrations of prostaglandins.RESULTS: IGML (%) and grade 3 (%) were 23.18±6.82, 58.44±9.07 in NS group, 4.42±1.39, 20.32±6.95 in SEF group and 3.74±1.56, 23.12±5.09 in CI group, and theabove parameters in SEF group and CI group decreased significantly (IGML: SEF vs NS, t = 6.712, P = 0.000<0.01; CI vs NS, t= 6.943, P= 0.000<0.01; grade 3: SEF vs NS,t= 8.386, P= 0.000; CI vs NS, t= 8.411, P= 0.000), but the grade 0 and grade 1 damage in SEF group (22.05±5.96, 34.12±8.12) and CI group (18.54±4.82, 30.15±7.12) were markedly higher than those in NS group (3.01±1.01, 8.35±1.95; grade 0: SEF vs NS, t= 8.434,P = 0.000<0.01; CI vs NS, t = 7.950, P = 0.000<0.01;grade 1: SEF vs NS, t= 8.422, P= 0.000<0.01; CI vs NS,t = 8.448, P = 0.000<0.01). The intracellular calcium content (μg/mg) in SEF group (0.104±0.015) and CI group (0.102±0.010) was markedly lower than that in NS group(0.131±0.019, SEF vs NS, t= 2.463, P= 0.038<0.05; CIvs NS, t= 3.056, P= 0.017<0.05). The levels (pg/mg) ofPGE2, 6-keto-PGF1αand 6-keto-PGF1α/TXB2 were 540±183, 714±124, 17.38±5.93 in NS group and 581±168, 737±102, 19.04±8.03 in CI group, 760±192, 1 248±158, 33.42±9.24 in SEF group, and the above parameters in SEF group markedly raised (PGE2: SEF vs NS, t = 2.282, P = 0.046 <0.05; SEF vs CI, t = 2.265, P = 0.047<0.05; 6-ketoPGF1α: SEF vsNS, t= 6.583, P= 0.000<0.000; SEF vsCI,t = 6.708, P = 0.000<0.01; 6-keto-PGF1α/TXB2: SEF vs NS, t= 3.963, P= 0.003<0.001; SEF vs CI, t= 3.243,P = 0.009<0.01), whereas TXB2 level in SEF group (45.37±7.54) was obviously lower than that in NS group (58.28±6.74, t = 3.086, P = 0.014<0.05) and CI group (54.32±6.89, t = 2.265, P = 0.047<0.05). No significant difference was shown between NS group and CI group (PGE2: t= 0.414, P= 0.688>0.05; 6-keto-PGF1α: t= 0.310,P = 0.763>0.05; TXB2: t = 1.099, P = 0.298>0.05; 6-keto-PGF1α/TXB2: t = 0.372, P = 0.718>0.05).CONCLUSION: Both SEF and CI could inhibit reperfusion induced injury in gastric mucosa, but with different mechanisms. SEF could not only enhance the protective effect of gastric rnucosa, but also abate the injury factors, while CI can only abate the injury factors.
基金funded by Taiju Life Social Welfare Foundation(to HS).
文摘Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.
文摘Objective: It demonstrates the correlation of the viral hemorrhagic fever with kidney failure and the treatment as well as the outcome. Method: A PubMed search of the English literature from 1999 to 2019 was performed using “viral hemorrhagic fever, Case Report, Renal Failure” as the subject. The inclusion criteria were the following: 1) case report and case series of two or more patients;2) the report detailed the clinical presentation and reported the status of the renal system;3) the report described the management of renal failure if any;and 4) the etiology of the infection is known and is one of the known agents of viral hemorrhagic fever, listed on the centers of disease control website. We excluded infections related to vaccination related to viral hemorrhagic fever. Result: We found the mean age of these patients was 41.5. The male to female ratio was about 3.5:1. Dengue and Hantaviruses constituted 70.5% of patients. The overall mortality of the study cohort was 32.2%. Half of the patients had acute kidney injury and required renal replacement therapy. The chi-square statistic is 0.41;The p-value is 0.51;The chi-square statistic is 6.4254. Overall mortality was 32.3% in one cohort of 78 patients. The illness goes through several stages [1] [2] of clinical features and some viruses in the group have a high case fatality rate. Conclusions: Early diagnosis with aggressive supportive care is critical for improving clinical outcomes. Renal involvement is common. Amongst the cohort reviewed, of patients who had acute kidney injury, half of the patients required renal replacement support. However, some viruses cause greater kidney injury than others, for instance, kidney injury is more severe in Dengue hemorrhagic fevers when compared to Hantaviruses. Simultaneous management of public health by prevention and control of outbreaks is particularly important.
基金Natural Science Research Project of Henan Province Education Department(NO.2006310021)
文摘Objective To observe the intestinal mucosal injury and the change of TNF-αcontent in rabbits with hemorrhagic shock/reperfusion(HS-R)and the effects of ganoderma Lcidum polysaccharide(GLP)on them.Methods 30rabbits were made into hemorrhagic shock,then reperfused with different liquids.These rabbits were divided by random number table into three groups:sham operation group(Sham group),reperfusion with normal saline group(NS group),reperfusion with 1%GLP group(LS group).Bacterial translocation of blood and TNF-αcontent in serum were respectively observed at the time before shock,40 min after shock,40 min and 90 min after.TNF-αcontent in intestinal mucosa and the degree of intestinal mucosal injury were examined at 90 min post-resuscitation.Results 1 With the extension of reperfusion time,the positive rate of blood bacteria increased gradually in NS group,which was significantly higher than that of Sham group and LS group(P<0.05),meanwhile the degree of intestinal mucosal injury in NS group was more severe than that of Sham group and LS group too(P<0.05).2TNF-αcontent in serum of NS group and LS group were increased obviously compared with that before shock and in Sham group(P<0.05).TNF-αcontent in serum was further increased after reperfusion with NS,which was distinctly higher than that in LS group.TNF-αcontent in intestinal mucosa of NS group was significantly higher than that in LS group and Sham group too(P<0.05).Conclusion GLP can protect intestinal mucosa against HS-R injury,and its effects may relate with the change of TNF-αin hemorrhagic shock rabbits.
基金Supported by the Traditional Chinese Medicine Research Foundation, Zhejiang Province, China 2005C072
文摘AIM: To study the effect of albumin administration on lung injury in trauma/hemorrhagic shock (T/HS). METHODS: Sixty experimental animals were randomly divided into three groups: rats undergoing laparotomy without shock (T/SS); rats with T/HS and resuscitation with blood plus twice the volume of shed blood as Ringer’s lactate (RL), and rats with T/HS and resuscitation with blood plus additional 3 mL of 50 g/L human albumin. Expression of polymorphonuclear neutrophil (PMN) CD11b/CD18, intercellular adhesion molecule-1 (ICAM-1) of jugular vein blood and the severity of lung injuries [determined mainly by measuring activity of lung tissue myeloperoxidase (MPO) and lung injury score (LIS)] were measured after a 3-h recovery period. RESULTS: All three groups showed a significant difference in the expressions of CD11b/CD18, ICAM-1, and severity of lung injury. The expressions of CD11b/ CD18 in T/SS group, T/HS + RL group, T/HS + albumin group were 17.76% ± 2.11%, 31.25% ± 3.48%, 20.36% ± 3.21%, respectively (F = 6.25, P < 0.05). The expressions of ICAM-1 (U/mL) in T/SS group, T/ HS + RL group, T/HS + albumin group were 258.76 ± 98.23, 356.23 ± 65.6, 301.01 ± 63.21, respectively (F = 5.86, P < 0.05). The expressions of MPO (U/g) in T/SS group, T/HS + RL group, T/HS + albumin group were 2.53 ± 0.11, 4.63 ± 1.31, 4.26 ± 1.12, respectively (F = 6.26, P < 0.05). Moreover, LIS in T/HS + RL group, T/HS + albumin group was 2.62 ± 0.23, 1.25 ± 0.24, respectively. The expressions of CD11b/CD18, ICAM-1 and MPO in T/HS + RL group were significantly increased compared to T/SS group (P = 0.025, P = 0.036, P = 0.028,respectively). However, administration of 3 mL of 50 g/L albumin significantly down-regulated the expressions of CD11b/CD18, ICAM-1 and lung injury index (MPO and LIS) when compared with the T/HS + RL rats (P = 0.035, P = 0.046, P = 0.038, P = 0.012, respectively). CONCLUSION: The infusion of albumin during resuscitation period can protect lung from injury and decrease the expressions of CD11b/CD18, ICAM-1 in T/ HS rats.
基金financially supported by the Xingtai Key Research Plan Project(2021zc096)。
文摘Objective:The objective of this study was to investigate the effects and possible mechanisms of action of ginseng on cerebral vasospasm and early brain injury(EBI)following hemorrhagic stroke.Materials and Methods:Sprague-Dawley(SD)rats(n=48)were randomly divided into sham operation(sham group),subarachnoid hemorrhage(SAH)model(SAH group),normal saline(NS group),and Ginaton(Extract of Ginkgo Biloba Leaves Drops)intervention(gin group)groups.MCP-1 m RNA and tumor necrosis factor levels were detected using reverse transcription-polymerase chain reaction.The relative expression of m RNA was detected by Western blotting.Results:(1)Compared with the sham group,the SAH,NS,and gin groups had different degrees of neurological dysfunction.Compared with the SAH and NS groups,the neurological deficits in the gin group were significantly improved(P<0.05).(2)Compared with the sham group,the relative expression levels of MCP-1 m RNA in the SAH,NS,and gin groups were 5.1±0.9,3.4±0.6,and 2.5±0.4,respectively;the relative expression levels of m RNA were 13.3±2.4,11.2±1.8,and 3.8±0.6,respectively.(3)The apoptosis rates of brain tissue in the sham,SAH,NS,and gin groups were 4.8±0.7,54.2±10.3,50.1±7.4,and 28.4±4.5,respectively.(4)Western blot showed that the relative expression levels of toll-like receptor-4(TLR-4)protein in the sham,SAH,NS,and gin groups were 0.29±0.03,0.87±0.15,0.65±0.13,and 0.41±0.17,respectively;the relative expression levels of B protein were 0.21±0.04,0.96±0.14,0.73±0.18,and 0.30±0.05,respectively.Gin treatment could inhibit TLR-4 and nuclear factor-κB(NF-κB)protein expression.Conclusions:Dona tablets may inhibit activation of the NF-κB signaling pathway,and SAH-induced inflammatory response,so as to reduce cerebral vasospasm and EBI.
基金supported by a Grant-in-Aid for Scientific Research from Novartis Pharmaceuticals to HS
文摘Aneurysmal subarachnoid hemorrhage remains devastating,and the most important determinant of poor outcome is early brain injury(EBI).In clinical settings,as a surrogate marker of EBI,loss of consciousness at ictus,poor initial clinical grades,and some radiographic findings are used,but these markers are somewhat subjective.Thus,it is imperative to find biomarkers of EBI that have beneficial prognostic and therapeutic implications.In our opinion,an ideal biomarker is a molecule that is implicated in the pathogenesis of both EBI and subsequently developing delayed cerebral ischemia(DCI),being a therapeutic target,and can be measured easily in the peripheral blood in an acute stage.A good candidate of such a biomarker is a matricellular protein,which is a secreted,inducible and multifunctional extracellular matrix protein.There are many kinds of matricellular proteins reported,but only tenascin-C,osteopontin,galectin-3 and periostin are reported relevant to EBI and DCI.Reliable biomarkers of EBI may stratify aneurysmal subarachnoid hemorrhage patients into categories of risk to develop DCI,and allow objective monitoring of the response to treatment for EBI and earlier diagnosis of DCI.This review emphasizes that further investigation of matricellular proteins as an avenue for biomarker discovery is warranted.
基金supported by the Natural Science Foundation of Anhui Province of China,No.1508085QH184(to YW)
文摘The Wnt/Frizzled signaling pathway participates in many inflammation-linked diseases. However, the inflammatory response mediated by the Wnt/Frizzled signaling pathway in experimental subarachnoid hemorrhage has not been thoroughly investigated. Consequently, in this study, we examined the potential role of the Wnt/Frizzled signaling pathway in early brain injury in rat models of subarachnoid hemorrhage.Simultaneously, possible neuroprotective mechanisms were also investigated. Experimental subarachnoid hemorrhage rat models were induced by injecting autologous blood into the prechiasmatic cistern. Experiment 1 was designed to examine expression of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. In total, 42 adult rats were divided into sham(injection of equivalent volume of saline), 6-, 12-, 24-, 48-, 72-hour, and 1-week subarachnoid hemorrhage groups. Experiment 2 was designed to examine neuroprotective mechanisms of the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage. Rats were treated with recombinant human Wnt1(rhwnt1), small interfering Wnt1(siwnt1) RNA, and monoclonal antibody of Frizzled1(anti-Frizzled1) at 48 hours after subarachnoid hemorrhage. Expression levels of Wnt1, Frizzled1, β-catenin, peroxisome proliferator-activated receptor-γ, CD36, and active nuclear factor-κB were examined by western blot assay and immunofluorescence staining. Microglia type conversion and inflammatory cytokine levels in brain tissue were examined by immunofluorescence staining and enzyme-linked immunosorbent assay. Our results show that compared with the sham group, expression levels of Wnt1, Frizzled1, and β-catenin were low and reduced to a minimum at 48 hours, gradually returning to baseline at 1 week after subarachnoid hemorrhage. rhwnt1 treatment markedly increased Wnt1 expression and alleviated subarachnoid hemorrhage-induced early brain injury(within 72 hours), including cortical cell apoptosis, brain edema, and neurobehavioral deficits, accompanied by increasing protein levels of β-catenin, CD36, and peroxisome proliferator-activated receptor-γ and decreasing protein levels of nuclear factor-κB. Of note, rhwnt1 promoted M2-type microglia conversion and inhibited release of inflammatory cytokines(interleukin-1β, interleukin-6, and tumor necrosis factor-α). In contrast, siwnt1 RNA and anti-Frizzled1 treatment both resulted in an opposite effect. In conclusion, the Wnt/Frizzled1 signaling pathway may participate in subarachnoid hemorrhage-induced early brain injury via inhibiting the inflammatory response, including regulating microglia type conversion and decreasing inflammatory cytokine release. The study was approved by the Animal Ethics Committee of Anhui Medical University and First Affiliated Hospital of USTC,Division of Life Sciences and Medicine, University of Science and Technology of China(approval No. LLSC-20180202) in May 2017.
基金supported by grants from the National Natural Science Foundation of China(No.81360185)the Foundation of the First Affiliated Hospital of Medical College of Shihezi University of China(No.SS2011-095)
文摘Early brain injury(EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage(SAH). This study investigated the role of glucose-regulated protein 78(GRP78) in EBI after SAH. Male Sprague-Dawley rats(n=108) weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated d UTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.
基金financially supported by the National Natural Science Foundation of China,No.81471179(to JNS)
文摘The role of vascular endothelial growth factor A in platelet adhesion in cerebral microvessels in the early stage of subarachnoid hemorrhage remains unclear.In this study,the endovascular puncture method was used to produce a rat model of subarachnoid hemorrhage.Then,30 minutes later,vascular endothelial growth factor A antagonist anti-vascular endothelial growth factor receptor 2 antibody,10μg,was injected into the right ventricle.Immunohistochemistry and western blot assay were used to assess expression of vascular endothelial growth factor A,occludin and claudin-5.Immunohistochemical double labeling was conducted to examine co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen.TUNEL was used to detect apoptosis in the hippocampus.Neurological score was used to assess behavioral performance.After subarachnoid hemorrhage,the expression of vascular endothelial growth factor A increased in the hippocampus,while occludin and claudin-5 expression levels decreased.Co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells increased,whereas behavioral performance was markedly impaired.After treatment with anti-vascular endothelial growth factor receptor 2 antibody,occludin and claudin-5 expression recovered,while co-expression of GP Ⅰa-Ⅱ integrin and type Ⅳ collagen and the number of apoptotic cells decreased.Furthermore,behavioral performance improved notably.Our findings suggest that increased vascular endothelial growth factor A levels promote platelet adhesion and contribute to early brain injury after subarachnoid hemorrhage.This study was approved by the Biomedical Ethics Committee,Medical College of Xi’an Jiaotong University,China in December 2015.